Activation of the P2Y1 receptor induces apoptosis and inhibits proliferation of prostate cancer cells

Wei, Qiang; Costanzi, Stefano; Liu, Qiu-Zhen; Gao, Zhan‐Guo; Jacobson, Kenneth A.

doi:10.1016/j.bcp.2011.05.013

Cited by 44 publications

(37 citation statements)

References 33 publications

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“…Previous studies showed a growth-inhibitory effect of both ATP and adenosine on PCa cells (13,15,16,(31)(32)(33). Corresponding to those findings, a growth-inhibitory effect of ATP and adenosine was observed on various PCa cell lines used in this study, including LNCaP, C4-2, C4-2B, DU145 and PC3, in a dose-dependent manner ( Figure 1).…”

Section: Discussionsupporting

confidence: 88%

Purinergic Receptor Expression and Cellular Responses to Purinergic Agonists in Human Prostate Cancer Cells

Lertsuwan

Peters

Johnson

et al. 2017

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Extracellular nucleotides were first proposed as signaling molecules in 1972 (1). Signaling through purinergic receptors is ubiquitous due to the diversity of purine and pyrimidine ligands, the number of receptors and extracellular nucleotidases. Purinergic signaling has been shown to play a role in many pathways including neurotransmission (2), cell differentiation, hormone secretion, vasodilation, cell proliferation, wound healing and apoptosis (3). There are two distinct families of purinergic receptors: P1 receptors for adenosine and P2 receptors for ATP/ADP and UTP/UDP ligands. P2 receptors are further divided into ligand-gated ion channel receptors, P2X, and G protein-coupled receptor, P2Y, subfamilies. To date, four P1 receptors (A 1,2a,2b,3 ), seven P2X receptors (P2X 1-7 ) and eight P2Y receptors (P2Y 1,2,4,6,11-14 ) have been identified in mammalian cells (4). The adenosine receptor subtypes A 1 and A 3 downregulate the production of cAMP, while A 2a and A 2b subtypes up-regulate the production of cAMP. Activation of P2X receptors leads to an influx of cations from the extracellular space, while activation of P2Y receptors leads to either an elevation of intracellular Ca 2+ from endoplasmic reticulum stores or down-regulation of cAMP production depending on the specific subtype of P2Y receptor activated.Growth suppression by the P2 agonist, ATP, was demonstrated first by Rapaport in 1983 (5). Exogenous ATP was shown to suppress the growth of pancreatic and colon cancer by causing cell-cycle arrest in S-phase. To date, the anticancer activity of extracellular nucleotides has been investigated in many types of cancer, including leukemia, melanoma and non-melanoma skin cancer, colorectal cancer, lung cancer, cervical cancer, prostate cancer (PCa) and squamous cell skin cancer (6). These led to clinical trials in patients with colorectal and non-small cell lung cancer that showed promising results with limited side-effects (7-9).PCa is the most frequently diagnosed cancer in North American men and the second leading cause of cancerrelated death in American men. It was estimated that there would be approximately 180,890 new cases of PCa and 26,5120 related deaths in the United States alone in 2016 (10). Current standard treatments for advanced PCa include various hormonal therapies whose goal is the ablation of androgens and their action (11). Even though 70% to 80% of patients respond well to first-line treatment, most patients eventually develop castrate-resistant disease (CRPCa) (12). Novel therapy therefore is needed to eliminate both early and 529 Τhis article is freely accessible online.

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Section: Discussionsupporting

confidence: 88%

Purinergic Receptor Expression and Cellular Responses to Purinergic Agonists in Human Prostate Cancer Cells

Lertsuwan

Peters

Johnson

et al. 2017

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“…Figure 4a shows that NECA (1 μM) decreases CHX-induced LDH release. It has been shown previously that the selective P2Y 1 receptor agonist MRS2365 (1 μM) enhanced the effect of CHX to promote LDH release in PC-3 cells [4]. Here, we have shown that the MRS2365-induced enhancement of CHXinduced LDH release was also diminished by NECA (Fig.…”

Section: Resultssupporting

confidence: 71%

“…In addition to the high expression level of the A 2B AR, P2Y 1 receptors [4], which are activated by endogenous adenine nucleotides, and ectonucleotidases CD39 and CD73 [19], which together degrade adenine nucleotides to produce adenosine, are also abundantly expressed in prostate cancer cells. Stagg et al [20] recently reported that CD73 deficiency suppressed prostate tumorigenesis in a mouse transgenic model of prostate cancer.…”

Section: Discussionmentioning

confidence: 99%

“…The assay method was previously described [4]. Briefly, cells were seeded in 96-well plates at a concentration of approximately 5,000 cells per well in 100 μl medium and cultured at 37°C overnight.…”

Section: Measurement Of Cell Growthmentioning

confidence: 99%

“…G protein-coupled receptors (GPCRs) are emerging targets for cancer [2,3]. We recently reported that agonists of the G protein-coupled P2Y 1 receptor could be potential novel drugs for prostate cancer [4]. It has been reported that the A 2B adenosine receptor (AR) is one of those most abundantly expressed in the human prostate cancer cells [5].…”

Section: Introductionmentioning

confidence: 99%

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A2B adenosine receptor blockade inhibits growth of prostate cancer cells

Wei

Costanzi

Balasubramanian

et al. 2013

Purinergic Signalling

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The role of the A 2B adenosine receptor (AR) in prostate cell death and growth was studied. The A 2B AR gene expression quantified by real-time quantitative RT-PCR and Western blot analysis was the highest among four AR subtypes (A 1 , A 2A , A 2B , and A 3 ) in all three commonly used prostate cancer cell lines, PC-3, DU145, and LNCaP. We explored the function of the A 2B AR using PC-3 cells as a model. The A 2B AR was visualized in PC-3 cells by laser confocal microscopy. The nonselective A 2B AR agonist NECA and the selective A 2B

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Neurogenic Differentiation of Mesenchymal Stem Cells Induces Alterations in Extracellular Nucleotides Metabolism

et al. 2016

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The presented results show for the first time that the neurogenic transdifferentiation of hUC-MSCs considerably changes the elements of purinergic signaling profile. Although, it has been demonstrated in the literature that extracellular nucleotides and nucleosides determine the fate of mesenchymal and neural stem cells, there is lack of comprehensive studies on the activity of ecto-enzymes metabolizing nucleotides on the surface of neurogenically induced cells. Our study shows that human UC-MSCs sense the microenvironment and adjust their response to the environmental signals for example, adenine nucleotides and nucleosides. Nucleotides, and not adenosine, signaling alters the biological potential of MSCs-decreases their proliferation rate, increases the neurogenic transdifferentiation efficiency expressed as the number of positively labeled NCAM and A2B5 cells and simultaneously increases the ecto-nucleotidases activity on neural- and glial-committed precursors. Purines implication in the proliferative and neurogenic potential of hUC-MSCs is of strong importance for the in vitro propagation of hUC-MSCs and for their successive therapeutic applications. J. Cell. Biochem. 118: 478-486, 2017. © 2016 Wiley Periodicals, Inc.

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Activation of the P2Y1 receptor induces apoptosis and inhibits proliferation of prostate cancer cells

Cited by 44 publications

References 33 publications

Purinergic Receptor Expression and Cellular Responses to Purinergic Agonists in Human Prostate Cancer Cells

Purinergic Receptor Expression and Cellular Responses to Purinergic Agonists in Human Prostate Cancer Cells

A2B adenosine receptor blockade inhibits growth of prostate cancer cells

Neurogenic Differentiation of Mesenchymal Stem Cells Induces Alterations in Extracellular Nucleotides Metabolism

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